Ferroptosis is a form of regulated cell death characterized by massive iron accumulation and iron-dependent lipid peroxidation,differing from apoptosis,necroptosis,and autophagy in several aspects.Ferroptosis is regar...Ferroptosis is a form of regulated cell death characterized by massive iron accumulation and iron-dependent lipid peroxidation,differing from apoptosis,necroptosis,and autophagy in several aspects.Ferroptosis is regarded as a critical mechanism of a series of pathophysiological reactions after stroke because of iron overload caused by hemoglobin degradation and iron metabolism imbalance.In this review,we discuss ferroptosis-related metabolisms,important molecules directly or indirectly targeting iron metabolism and lipid peroxidation,and transcriptional regulation of ferroptosis,revealing the role of ferroptosis in the progression of stroke.We present updated progress in the intervention of ferroptosis as therapeutic strategies for stroke in vivo and in vitro and summarize the effects of ferroptosis inhibitors on stroke.Our review facilitates further understanding of ferroptosis pathogenesis in stroke,proposes new targets for the treatment of stroke,and suggests that more efforts should be made to investigate the mechanism of ferroptosis in stroke.展开更多
BACKGROUND Despite significant advancements in the medical treatment of primary hepato-cellular carcinoma(PHC)in recent years,enhancing therapeutic effects and im-proving prognosis remain substantial challenges worldw...BACKGROUND Despite significant advancements in the medical treatment of primary hepato-cellular carcinoma(PHC)in recent years,enhancing therapeutic effects and im-proving prognosis remain substantial challenges worldwide.AIM To investigate the expression levels of serum vascular endothelial growth factor(VEGF)and interleukin(IL)-17 in patients with PHC and evaluate their diagnostic value while exploring their relationship with patients’clinical characteristics.METHODS The study included 50 patients with confirmed PHC who visited Wuhan Han-yang Hospital from January 2021 to January 2022,and 50 healthy individuals from the same period served as the control group.Serum VEGF and IL-17 levels in both groups were measured by Enzyme-Linked Immunosorbent Assay,and their diagnostic value was assessed using receiver operating characteristic(ROC)curves.Pearson correlation analysis was performed to examine the relationship between serum VEGF and IL-17 levels.Pathological data of the PHC patients were analyzed to determine the relationship between serum VEGF and IL-17 levels and pathological characteristics.RESULTS Serum VEGF and IL-17 levels were significantly higher in the study group com-pared to the control group(P<0.05).No significant association was observed between serum VEGF and IL-17 levels and gender,age,combined cirrhosis,tumor diameter,or degree of differentiation(P>0.05).However,there was a significant relationship between clinical TNM stage,tumor metastasis,and serum VEGF and IL-17 levels(P<0.05).Correlation analysis revealed a positive correlation between serum VEGF and IL-17(P<0.05).ROC analysis demonstrated that both serum VEGF and IL-17 had good diagnostic efficacy for PHC.CONCLUSION Serum VEGF and IL-17 levels were significantly higher in PHC patients compared to healthy individuals.Their levels were closely related to pathological features such as tumor metastasis and clinical TNM stage,and there was a significant positive correlation between VEGF and IL-17.These biomarkers may serve as valuable reference in-dicators for the early diagnosis and treatment guidance of PHC.展开更多
Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro...Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.展开更多
Objective To explore the role and regulation of guanine nucleotide-binding protein G（i）, a-1 subunit （GNAI1） in hepatocellular carcinoma （HCC）. Methods Expression of GNAI1 in HCC samples was determined by qRT-PC...Objective To explore the role and regulation of guanine nucleotide-binding protein G（i）, a-1 subunit （GNAI1） in hepatocellular carcinoma （HCC）. Methods Expression of GNAI1 in HCC samples was determined by qRT-PCR and immunohistochemical （IHC） staining. Huh-7 and SNU-387 cells stably expressing GNAI1 were established by the infection of lentivirus transducing unit containing GNAI1. siRNA against GNAI1 was transfected into SMMC-7721 cells to knock down the GNAI1 expression in HCC cells. Mir-320a/c/d mimics were transfected into SMMC-7721 and SK-Hep-1 cells and the expression of GNAll was determined by Western blot. The migration and invasion of Huh-7, SNU-387, SK-Hep-1 and SMMC-7721 cells were investigated by Transwell assays. Results The GNAI1 protein was significantly downregulated in HCC samples without changes in its mRNA levels. GNAI1 could inhibit the migration and invasion of HCC cells in vitro. Further investigations indicated that GNAI1 was a target of miR-320a/c/d in HCC cells. Transwell assays demonstrated that these microRNAs could promote the migratory ability and invasivesess of HCC cells in vitro. Conclusions GNAII is downregulated in HCC and inhibits the migration and invasion of HCC cells. This study is the first to investigate the role of GNAI1 in cancer. Regulation of GNAI1 by miR-320a/c/d indicates new therapeutic avenues for targeting HCC metastasis.展开更多
This paper presents an analytical solution for one-dimensional consolidation of soft soil under some common types of cyclic loading such as trapezoidal cyclic loading, based on the assumptions proposed by Davis and Ra...This paper presents an analytical solution for one-dimensional consolidation of soft soil under some common types of cyclic loading such as trapezoidal cyclic loading, based on the assumptions proposed by Davis and Raymond （1965） that the decrease in permeability is proportional to the decrease in compressibility during the consolidation process of the soil and that the distribution of initial effective stress is constant with depth the solution obtained, some diagrams are prepared and the It is verified by the existing analytical solutions in special cases. Using telex ant consolidation behavior is investigated.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81971870 and 82172173(to ML).
文摘Ferroptosis is a form of regulated cell death characterized by massive iron accumulation and iron-dependent lipid peroxidation,differing from apoptosis,necroptosis,and autophagy in several aspects.Ferroptosis is regarded as a critical mechanism of a series of pathophysiological reactions after stroke because of iron overload caused by hemoglobin degradation and iron metabolism imbalance.In this review,we discuss ferroptosis-related metabolisms,important molecules directly or indirectly targeting iron metabolism and lipid peroxidation,and transcriptional regulation of ferroptosis,revealing the role of ferroptosis in the progression of stroke.We present updated progress in the intervention of ferroptosis as therapeutic strategies for stroke in vivo and in vitro and summarize the effects of ferroptosis inhibitors on stroke.Our review facilitates further understanding of ferroptosis pathogenesis in stroke,proposes new targets for the treatment of stroke,and suggests that more efforts should be made to investigate the mechanism of ferroptosis in stroke.
文摘BACKGROUND Despite significant advancements in the medical treatment of primary hepato-cellular carcinoma(PHC)in recent years,enhancing therapeutic effects and im-proving prognosis remain substantial challenges worldwide.AIM To investigate the expression levels of serum vascular endothelial growth factor(VEGF)and interleukin(IL)-17 in patients with PHC and evaluate their diagnostic value while exploring their relationship with patients’clinical characteristics.METHODS The study included 50 patients with confirmed PHC who visited Wuhan Han-yang Hospital from January 2021 to January 2022,and 50 healthy individuals from the same period served as the control group.Serum VEGF and IL-17 levels in both groups were measured by Enzyme-Linked Immunosorbent Assay,and their diagnostic value was assessed using receiver operating characteristic(ROC)curves.Pearson correlation analysis was performed to examine the relationship between serum VEGF and IL-17 levels.Pathological data of the PHC patients were analyzed to determine the relationship between serum VEGF and IL-17 levels and pathological characteristics.RESULTS Serum VEGF and IL-17 levels were significantly higher in the study group com-pared to the control group(P<0.05).No significant association was observed between serum VEGF and IL-17 levels and gender,age,combined cirrhosis,tumor diameter,or degree of differentiation(P>0.05).However,there was a significant relationship between clinical TNM stage,tumor metastasis,and serum VEGF and IL-17 levels(P<0.05).Correlation analysis revealed a positive correlation between serum VEGF and IL-17(P<0.05).ROC analysis demonstrated that both serum VEGF and IL-17 had good diagnostic efficacy for PHC.CONCLUSION Serum VEGF and IL-17 levels were significantly higher in PHC patients compared to healthy individuals.Their levels were closely related to pathological features such as tumor metastasis and clinical TNM stage,and there was a significant positive correlation between VEGF and IL-17.These biomarkers may serve as valuable reference in-dicators for the early diagnosis and treatment guidance of PHC.
基金supported by the National Natural Science Foundation of China,Nos.81971870,82172173(both to MCL)。
文摘Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.
基金supported by grants from the National 973 Key Basic Research Program(No.2011CB933100)National Natural Science Foundation of China(No.81125016 and 81101481)+1 种基金Science and Technology Commission of Shanghai Municipality(No.11XD1404500 and 10JC1414200)Shanghai Health Bureau(No.XYQ2011047 and XBR2011039)
文摘Objective To explore the role and regulation of guanine nucleotide-binding protein G（i）, a-1 subunit （GNAI1） in hepatocellular carcinoma （HCC）. Methods Expression of GNAI1 in HCC samples was determined by qRT-PCR and immunohistochemical （IHC） staining. Huh-7 and SNU-387 cells stably expressing GNAI1 were established by the infection of lentivirus transducing unit containing GNAI1. siRNA against GNAI1 was transfected into SMMC-7721 cells to knock down the GNAI1 expression in HCC cells. Mir-320a/c/d mimics were transfected into SMMC-7721 and SK-Hep-1 cells and the expression of GNAll was determined by Western blot. The migration and invasion of Huh-7, SNU-387, SK-Hep-1 and SMMC-7721 cells were investigated by Transwell assays. Results The GNAI1 protein was significantly downregulated in HCC samples without changes in its mRNA levels. GNAI1 could inhibit the migration and invasion of HCC cells in vitro. Further investigations indicated that GNAI1 was a target of miR-320a/c/d in HCC cells. Transwell assays demonstrated that these microRNAs could promote the migratory ability and invasivesess of HCC cells in vitro. Conclusions GNAII is downregulated in HCC and inhibits the migration and invasion of HCC cells. This study is the first to investigate the role of GNAI1 in cancer. Regulation of GNAI1 by miR-320a/c/d indicates new therapeutic avenues for targeting HCC metastasis.
基金Projects supported by the National Research Foundation for theDoctoral Program of Higher Education of China (No. 20030335027)and the Natural Science Foundation of Zhejiang Province (No.Y104463), China
文摘This paper presents an analytical solution for one-dimensional consolidation of soft soil under some common types of cyclic loading such as trapezoidal cyclic loading, based on the assumptions proposed by Davis and Raymond （1965） that the decrease in permeability is proportional to the decrease in compressibility during the consolidation process of the soil and that the distribution of initial effective stress is constant with depth the solution obtained, some diagrams are prepared and the It is verified by the existing analytical solutions in special cases. Using telex ant consolidation behavior is investigated.
